Low on energy? An energy supply-demand perspective on stress and depression

•Reduced ATP or oxygen availability is common in depression models, human depression, and depression risk factors.•Capillary dysfunction can cause tissue hypoxia, even when blood supply is inconspicuous.•Tissue hypoxia triggers inflammation, affecting capillary function in other organs.•Inflammatory cytokines and tissue hypoxia interfere with neurotransmitter synthesis.•Early life stress may predispose to depression and other diseases in later life by damaging the splanchnic microcirculation.•Capillary function and neurogenic blood flow affect brain oxygenation, and whether functional neuroimaging truly detects changes in neuronal activity.